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PMID: 19712078 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

The bacterial virulence factor NleA is required for the disruption of intestinal tight junctions by enteropathogenic Escherichia coli.

Cellular microbiology ·Vol. 12 ·No. 1 ·2010-01-00 ·Pages 31-41

Thanabalasuriar A, Koutsouris A, Weflen A, Mimee M, Hecht G, Gruenheid S

Abstract

Enteropathogenic Escherichia coli (EPEC) is a diarrhoeal pathogen that adheres to epithelial cells of the small intestine and uses a type III secretion system to inject effector proteins into host cells. EPEC infection leads to disruption of host intestinal tight junctions that are important for maintaining intestinal barrier function. This disruption is dependent on the bacterial type III secretion system, as well as the translocated effectors EspF and Map. Here we show that a third type III translocated bacterial effector protein, NleA, is also involved in tight junction disruption during EPEC infection. Using the drug Brefeldin A, we demonstrate that the effect of NleA on tight junction integrity is related to its inhibition of host cell protein trafficking through COPII-dependent pathways. These results suggest that NleA's striking effect on virulence is mediated, at least in part, via its role in disruption of intestinal barrier function.

MeSH Terms
Brefeldin A/pharmacology Caco-2 Cells Carrier Proteins/genetics,metabolism,physiology Cell Line, Tumor Endoplasmic Reticulum/drug effects,metabolism Enteropathogenic Escherichia coli/pathogenicity,physiology Escherichia coli Proteins/genetics,metabolism,physiology Genetic Complementation Test Golgi Apparatus/drug effects,metabolism HeLa Cells Humans Intestines/microbiology Intracellular Signaling Peptides and Proteins Microscopy, Fluorescence Tight Junctions/metabolism Two-Hybrid System Techniques Virulence/genetics,physiology Virulence Factors/genetics,metabolism,physiology
Chemicals
Carrier Proteins Escherichia coli Proteins EspFU protein, E coli Intracellular Signaling Peptides and Proteins Map protein, E coli NleA protein, E coli Virulence Factors Brefeldin A
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Thanabalasuriar Ajitha
Department of Microbiology and Immunology, The McGill Life Sciences Complex, Montreal, Quebec, Canada.
Koutsouris Athanasia
Weflen Andrew
Mimee Mark
Hecht Gail
Gruenheid Samantha
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Article Info
Journal
Cellular microbiology
Abbr.
Cell Microbiol
ISSN
1462-5822
DOI
10.1111/j.1462-5822.2009.01376.x
Published
2010-01-00
Epub
2009-00-27
Pages
31-41
Language
English
Region
England
NLM ID
100883691
PMCID
PMC2850276
Subset
IM
Grants
NIDDK NIH HHS · R01 DK050694-12 · United States
NIDDK NIH HHS · P01 DK067887 · United States
NIDDK NIH HHS · R56 DK050694 · United States
NIDDK NIH HHS · P01 DK067887-039002 · United States
CIHR · Canada
NIDDK NIH HHS · DK58964 · United States
NIDDK NIH HHS · DK50694 · United States
NIDDK NIH HHS · P01 DK067887-03 · United States
NIDDK NIH HHS · R01 DK058964-08 · United States
NIDDK NIH HHS · P01 DK067887-04 · United States
NIDDK NIH HHS · R01 DK058964 · United States
NIDDK NIH HHS · R01 DK050694 · United States
NIDDK NIH HHS · R01 DK058964-07 · United States
NIDDK NIH HHS · R01 DK050694-13 · United States
NIDDK NIH HHS · P01 DK067887-049002 · United States
External Links
PubMed source DOI: 10.1111/j.1462-5822.2009.01376.x PMC Full Text View journal details
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